奥拉帕尼二聚体杂质的合成

Synthesis of olaparib dimer impurity

目的研究抗肿瘤药物奥拉帕尼二聚体的合成。方法以(3-氧代-1,3-二氢异苯并呋喃-1-基)膦酸二甲酯为原料,与2-氟-5-甲酰基苯腈反应,再经过水解、环合,最后与哌嗪反应得到奥拉帕尼二聚体杂质,并经过^(1)H-NMR、MS等进行了结构确证。结果合成了奥拉帕尼二聚体杂质,为建立质量标准所需的对照品提供了参考。结论合成奥拉帕尼二聚体杂质使用的各种原料经济易得,合成工艺简单,反应条件温和,反应操作简单,所得产品收率和纯度均较高,合成路线可行。

Objective To study the synthesis of the dimer of the antineoplastic drug Olaparib.Methods Olaparib dimer impurity was obtained from 3-oxo-1,3-dihydroisoben-zofuran-1-ylphosphonic acid by reacting with 2-fluoro-5-formylbenzonitrile,hydrolysis,cyclization,and finally with piperazine,and their structures were confirmed by ^(1)H-NMR and MS.Results Olaparib dimer impurity was synthesized,which provided reference for establishing quality standard.Conclusion Various raw materials for the synthesis of olaparib dimer impurity are economical and easy to obtain.The synthetic process is simple,the reaction conditions are mild,and the operation is simple.The yield and purity of the product are high.The synthetic route is feasible.